Blood oxygen level dependent MRI was used to test whether cocaine-stimulated mesolimbic activity varied with sexual receptivity. Rats were randomly screened for lordotic responses and were then imaged for their responses to centrally administered cocaine. We observed that female rats expressing no lordosis showed a greater activation of mesolimbic and nigrostriatal structures than lordotic female rats. Our data suggest that the differential sensitivity to cocaine occurs not only as a result of hormonal changes of the estrous cycle, but also in association with changes in sexual receptivity.